Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation,☆☆,,★★

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Abstract

To infer possible mechanisms of acute airway inflammation and mucus hypersecretion in acute severe asthma, we performed cellular and biochemical analysis on sputum from 18 adults with acute severe asthma and compared the results with results of analysis of sputum from 12 adults with cystic fibrosis (CF). We found that in subjects with asthma neutrophils made up more than 75% of sputum cells in 10 samples whereas eosinophils made up more than 75% of cells in only three samples. Fifty percent of the subjects with asthma reported that their asthma exacerbation was precipitated by a respiratory tract infection, and these subjects had a significantly higher percentage of neutrophils in their sputum (85% ± 6% vs 57% ± 12%, p = 0.05). In the CF samples neutrophils made up more than 95% and eosinophils less than 1% of cells in all samples analyzed. Analysis of fluid phase chemicals in asthmatic and CF sputum samples showed that despite overall lower mean values of neutrophil elastase (27 ± 11 μg/ml vs 466 ± 121 μg/ml, p = 0.0001) and interleukin-8 (IL-8) (55 ± 15 ng/ml vs 186 ± 24 ng/ml, p = 0.0001), some of the asthmatic samples had values for these variables that overlapped those in the CF samples. In addition, the asthmatic samples were distinguished by the presence of higher tryptase (10 ± 7 U/L vs 0.9 ± 0.9 U/L, p = 0.0001) and interleukin-6 (1166 ± 447 ng/ml vs 186 ± 24 ng/ml; p = 0.0001) levels and by a higher ratio of albumin to mucin-like glycoprotein (0.8 ± 0.5 vs 0.1 ± 0.002, p = 0.02). DNA levels were lower in the asthmatic samples (0.5 ± 0.3 mg/ml vs 3.5 ± 1.2 mg/ml, p = 0.05). We conclude that neutrophils predominate more frequently than eosinophils as the major inflammatory cell in sputum from patients with asthma in acute exacerbation. We speculate that this may be because respiratory tract infections are a frequent precipitant of acute asthma. In addition, the high IL-8 levels and free neutrophil elastase activity observed in asthmatic sputum suggests that IL-8 may mediate airway neutrophilia in acute asthma and that neutrophil elastase may mediate mucin glycoprotein hypersecretion in acute asthma, as has been proposed for the mucin hypersecretion in CF. (J ALLERGY CLIN IMMUNOL 1995;95:843-52.)

Section snippets

Subjects with asthma

Patients who had acute severe asthma diagnosed by emergency room physicians at San Francisco General Hospital and at Moffitt-Long Hospital at the University of California, San Francisco (UCSF) were invited to provide a sample of sputum and to complete a medical questionnaire. The medical questionnaire inquired about asthma history, asthma medications, concomitant illnesses (including allergies), history of cigarette smoking, events that triggered the current asthma attack, and the length of

RESULTS

We found that neutrophils rather than eosinophils were more frequently the predominant cell in sputum from patients with acute severe asthma (Table III, Fig. 1). Neutrophils made up more than 75% of the nonsquamous cells in 10 samples and constituted more than 90% of cells in five samples. Eosinophils made up more than 75% of the nonsquamous cells in only three samples but were identifiable in all asthmatic sputum samples at lower percentages. Eight of the 16 subjects with asthma (50%) who

DISCUSSION

In this study we analyzed the cellular and biochemical constituents of sputum from acutely ill subjects with asthma and compared the findings with those from analysis of sputum from patients with CF. Our main findings are that the predominant inflammatory cell in sputum from acutely ill subjects with asthma is more frequently the neutrophil than the eosinophil and that asthmatic sputum is also characterized by relatively high levels of DNA, albumin, and MLG. The pathophysiologic mechanisms

Acknowledgements

We thank Carol Basbaum, PhD, and Walter Finkbeiner, MD for providing us with the A10G5 monoclonal antibody, and Alan Gelb, MD; Susan K. Ulrich, MS, RN; and Virginia Hill, RN, for assistance in the collection of sputum samples and characterization of the subjects.

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  • Cited by (0)

    From the aDepartment of Medicine and the bCardiovascular Research Institute, University of California, San Francisco.

    ☆☆

    Supported by Program Project grant HL 24136 from the National Institutes of Health and by NRSA grant HL07185 (J.V.F.).

    Reprint requests: John V. Fahy, MD, Box 0130, University of California, San Francisco, 505 Parnassus Ave., San Francisco, CA 94143,

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